A number of inorganic materials have been shown to possess antimicrobial activity. They include metal ions such as silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium and thallium ions. It is theorized that these antimicrobial metal ions exert their effects by disrupting respiration and electron transport systems upon absorption into bacterial or fungal cells. Antimicrobial metal ions of silver, copper, zinc, and gold, in particular, are considered safe for in vivo use. Antimicrobial silver ions are particularly useful for in vivo uses due to the fact that they have the highest ratio of efficacy to toxicity.
Antimicrobial zeolites can be prepared by replacing all or part of the ion-exchangeable ions in zeolite with antimicrobial metal ions, as described in U.S. Pat. Nos. 4,911,898; 4,911,899; 4,938,955; 4,906,464; and 4,775,585.
Zirconium compounds, such as zirconium phosphates, have also been modified to provide antimicrobial characteristics, as described in U.S. Pat. Nos. 4,025,608 and 4,059,679. J. Antibact. Antifung. Agents Vol. 22, No. 10, pp. 595-601, 1994 and references therein describe the antimicrobial characteristics of zirconium phosphate ceramics.
Antimicrobial water soluble glasses have been used and are described in U.S. Pat. No. 5,470,585.
Antimicrobial hydroxyapatite powders have been prepared and are described in U.S. Pat. Nos. 5,009,898 and 5,268,174.
U.S. Pat. No. 4,775,585 discloses incorporating metal-zeolite into a polymer to obtain a polymer with bactericidal activity. U.S. Pat. No. 4,923,450 discloses incorporating zeolite in bulk materials for production of medical tubes. Dependent upon material selection and processing conditions, when zeolite is conventionally compounded into polymers, the zeolite often agglomerates, causing poor dispersion of the zeolite in the polymer. When such material is molded or extruded, the surface of the polymer is frequently beaded instead of flat. Poor dispersion of the zeolite also can cause changes in the bulk properties of the polymer, such as a reduction in tensile strength.
Furthermore, it has been found by the present inventors that conventionally compounding antimicrobial zeolites in many polymeric materials, dependent upon processing conditions and the particular polymer, can result in discoloration. This appears also to result from inadequate dispersion of the zeolite, i.e., the formation of zeolite aggregates in the material as well as from chemical reactions involving the antimicrobial metal ions and the polymer itself, e.g., additives, contaminants, residual catalysts, moisture, etc. in the polymer, and/or any air or water introduced during the compounding process.
In certain instances, these problems can be avoided by use of antimicrobial coatings. However, this requires an extra processing step and raises additional problems such as adherence and permanence of the coating.
U.S. Pat. No. 5,094,847 recognizes that in order to get the desired antibacterial activity, a large amount of zeolite powder must be added to the polyolefin resin and that this is accompanied by poorer appearance, lower physical properties and roughened surface appearance. They disclose using low levels of antimicrobial agent followed by a corona discharge treatment. This requires additional equipment and an extra processing step.
U.S. Pat. No. 5,614,568 discloses an antibacterial resin composition comprising a styrene resin, an antibacterial agent and a compound or polymer having at least one functional group and a molecular weight of 300 to 10,000. In order to obtain good antimicrobial activity, they require the use of low molecular weight compounds or low molecular weight polymers, which can have deleterious effects on properties.
U.S. Pat. No. 6,013,275 discloses a copolymer of an antibacterial agent and a hydrophilic substance. Copolymerization is an extra step, which adds to complexity and cost and limits the choice of both the hydrophilic substance and the antibacterial agent. The hydrophilic substance must have functional groups capable of reacting with and copolymerizing with the antibacterial agent. Similarly, the antibacterial agent must have reactive groups capable of forming a copolymer with the antibacterial agent.
WO 00/30697 discloses an antimicrobial coated substrate comprising an antimicrobial coating composition coated on a substrate. The antimicrobial coating composition comprises a hydrophilic polymer having antimicrobial ceramic particles dispersed therein. They require a coating process. This requires additional equipment and an extra processing step.
One of the problems in the prior art is the unavailability, for the most part, of that quantity of the antimicrobial agent which lies beneath the surface of the article or coating into which it is incorporated. Unless the antimicrobial agent migrates from the polymer matrix, a characteristic not common to inorganic, especially ion-exchange type, antimicrobial agents, the entombed antimicrobial agent is without utility or efficacy. This requires the use of a larger quantity of antimicrobial agents so as to provide a higher concentration at the surface, which is more costly and often imparts deleterious properties. There remains a need to provide an antimicrobial agent in a form that is suitable to impart antimicrobial properties without the accompanying problems of the prior art.
Another problem in the prior art is that while the use of hydrophilic coatings and polymer matrices may mitigate, at least in part, the foregoing problem, this beneficial improvement is limited to utility in the narrow class of hydrophilic coatings and polymers and, more importantly, the very limited end use applications for which such hydrophilic coatings and polymers are appropriate. Thus, there is also a need in the art to find a means by which antimicrobial agent entombed within a polymer coating or matrix can be accessed or available for providing antimicrobial efficacy regardless of polymer comprising the coating or matrix.
Yet another problem in the prior art is that the rate of release of the antimicrobial agent is determined by solubility of the antimicrobial agent or, in the case of the ion-exchange type antimicrobial agents, the ion-exchange rate of the ceramic carrier and the water exposure or flow across the surface containing the antimicrobial agent. In high moisture, especially high flow environments, for example, a dishwasher interior, a high solubility or ion-exchange rate may lead to a premature depletion of the antimicrobial agent; thus, greatly reducing the life time of the antimicrobial efficacy. Thus, there is also a need in the art to be able to control the release rate of the antimicrobial agent.